**Figure 9.** Fig. 6 Model depicting cascade of the anti-inflammatory effect of ciprofloxacin and levofloxacin, targeting TLR4–MD-2 complex. LBP facilitates transfer of LPS monomers to CD14, which subsequently shifts the endotoxin to TLR4/MD-2 complex, then leading to formation of TLR4/MD2/LPS ternary complex and its subsequently dimerization. Dimerization of the receptor complex induces the activation of intracellular signaling pathways that involve NF-κB activation and lead to production of pro-inflammatory cytokines (left panel). Fluoroquinolones, such as CPFX and LVFX, exert anti-inflammatory activity, through the inhibition of TLR4/MD2/LPS ternary complex formation, receptor dimerization, and NF-κB nuclear translocation (depicted in light colors in the right panel), resulting in a decreased production of pro-inflammatory cytokines. CD14 cluster of differentiation 14, CPFX ciprofloxacin, IL-1β interleukin-1 β, LBP LPS binding protein, LPS lipopolysaccharide, LVFX levofloxacin, MD-2 myeloid differentiation protein-2, TLR4 Toll-like receptor 4, TNF-α tumor necrosis factor-α

Descripción

Proposed mechanistic model depicts how ciprofloxacin and levofloxacin target the TLR4-MD-2 complex to block LPS-induced downstream signaling cascades and cytokine production.

More Figures from This Paper

Figure 4

Molecular docking analysis reveals two alternative binding conformations of ciprofloxacin within the TLR4-MD-2 complex binding pocket, suggesting direct physical interaction with the innate immune receptor.

diagram

Figure 5

Cell viability assays demonstrate that ciprofloxacin and levofloxacin at the tested concentrations do not significantly reduce microglial survival, confirming that anti-inflammatory effects are not due to cytotoxicity.

chart

Figure 6

Cytokine release profiles from LPS-stimulated cortical microglia reveal dose-dependent reductions in TNF-alpha and IL-6 following fluoroquinolone treatment.

chart

Figure 7

NF-kB nuclear translocation in LPS-stimulated microglia is attenuated by both ciprofloxacin and levofloxacin, as shown by immunofluorescence or reporter gene assays.

chart

Figure 8

LPS binding and TLR4 dimerization assays in Ba/F3 cells demonstrate that fluoroquinolones interfere with the initial receptor activation step of innate immune signaling.

chart

Figure 9

Diagram

935 × 326px · 167,8 KB

Source Paper

Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway.

Journal of neuroinflammation (2019)

PMID: 31319868

DOI: 10.1186/s12974-019-1538-9

Cite This Figure

![Figure 9: Proposed mechanistic model depicts how ciprofloxacin and levofloxacin target the TLR4-MD-2 complex to block LPS-induced downstream signaling cascades and cytokine production.](https://pdfs.citedhealth.com/figures/31319868/119.png)

> Source: Morena Zusso et al. "Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR." *Journal of neuroinflammation*, 2019. PMID: [31319868](https://pubmed.ncbi.nlm.nih.gov/31319868/)

<figure>
  <img src="https://pdfs.citedhealth.com/figures/31319868/119.png" alt="Proposed mechanistic model depicts how ciprofloxacin and levofloxacin target the TLR4-MD-2 complex to block LPS-induced downstream signaling cascades and cytokine production." />
  <figcaption>Figure 9. Proposed mechanistic model depicts how ciprofloxacin and levofloxacin target the TLR4-MD-2 complex to block LPS-induced downstream signaling cascades and cytokine production.<br>  Source: Morena Zusso et al. "Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR." <em>Journal of neuroinflammation</em>, 2019. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/31319868/">31319868</a></figcaption>
</figure>

Evidencia relacionada

Curcumin para Oxidative Stress & Neuroinflammation

Calificación B · 15 estudios